•  Sterility Assurance Levels

Relevance:

    •  Products with high sterility assurance levels provide higher protection against the presence of blood-borne pathogens and transmission of disease.

TEI Products:

    •  Our products are terminally sterilized via an ETO process, providing a 10-6 SAL (Sterility Assurance Level), eliminating the risk of blood-borne pathogens and transmission of disease. TEI’s manufacturing process also includes a viral inactivation step validated to ensure inactivation of potentially contaminating virus classes, including enveloped & non-enveloped RNA and enveloped & non-enveloped DNA virus.

Competitive Products:

    •  Many Acellular Dermal Matrix (ADM) products from other providers/manufacturers are minimally processed and/or bathed in antibiotics and as such do not provide the same level of sterility assurance as those from TEI. These products cannot guarantee lack of transfer of blood-borne pathogens, including all forms of hepatitis and/or HIV.

•  Processing

Relevance:

    •  Different tissue-processing methodologies can produce Acellular Dermal Matrix (ADM) devices with post-implantation responses that differ significantly, including:

        •  A classic foreign-body encapsulation similar to that of a permanent implant

        •  Rapid or slow degradation/resorption

        •  Population by local fibroblasts and supporting vasculature to generate new, metabolically active tissue

    •  ADMs that are minimally processed (i.e. tissue-banked products) are typically non-sterile, bathed in potentially antigenic antibiotics and preservatives and other retained components that the host perceives as ‘contaminants,’ leading to inflammation and, ultimately, the matrix’s degradation. This response results in only temporary tissue reinforcement.

    •  Although artificial chemical crosslinking was initially thought necessary to limit the foreign-body reaction to an implanted non-autologous tissue and preserve implant integrity, it is now appreciated that the latter can be achieved without the need for crosslinking.

    •  Only ADM processes that result in high sterility assurance levels and include a validated viral inactivation step eliminate the risk of blood-borne pathogens and transmission of disease.

    •  Sophisticated biotech processes now allow for ADMs to be lyophilized (freeze-dried), resulting in products that re-hydrate rapidly (1-2 minutes), have a multiple year shelf life, and require no refrigerated storage.

TEI Products:

    •  Our products are terminally sterilized via an ETO process, providing a 10-6 SAL (Sterility Assurance Levels), eliminating the risk of blood-borne pathogens and transmission of disease. TEI’s manufacturing process also includes a viral inactivation step validated to ensure inactivation of potentially contaminating virus classes, including enveloped & non-enveloped RNA and enveloped & non-enveloped DNA virus. Our process negates the need to bathe the ADM in antibiotics during processing and while packaged.

    •  TEI’s process incorporates a lyophilization (freeze-dry) process which generates a product that:

        •  requires no refrigeration

        •  offers up to five years of shelf life

        •  is highly porous, re-hydrating rapidly and quickly able to absorb the host’s blood, cells, growth factors, and cytokines at the time of implantation or application

    •  TEI’s sterilization, viral inactivation, and lyophilization steps eliminate the need for using potentially antigenic antibiotics and preservatives.

    •  TEI has found that it is possible to generate an ADM that persists, without the need to rely on crosslinking.

    •  When implanted or applied, our technology’s purity, sterility, and nativity minimize detrimental foreign-body inflammation to provide a matrix that is rapidly revascularized and repopulated with patient cells, generating new, metabolically active tissue that provides prolonged reinforcement during healing.

Competitive Products:

    •  A non-crosslinked ADM biomaterial derived from minimally processed human cadaveric dermis will experience degradation/resorption, impacting the tissue repair for which it was used.1,2

    •  Chemically-crosslinked ADMs will lead to recognition as a foreign body. The triggered host–implant interaction (encapsulation) is similar to that of a synthetic mesh.

1 Cornwell KG, Downing BR, Pins GD. Characterizing fibroblast migration on discrete collagen threads for applications in tissue regeneration. J Biomed Mater Res A 2004;71(1):55–62.

2 Cornwell KG, Lei P, Andreadis ST, et al. Crosslinking of discrete self-assembled collagen threads: effects on mechanical strength and cell-matrix interactions. J Biomed Mater Res A 2007;80(2):362–71.

•  Purity

Relevance:

An Acellular Dermal Matrix (ADM) that contains potentially antigenic antibiotics, preservatives, and/or other retained components that the host perceives as ‘contaminants’ could trigger a detrimental foreign-body inflammatory reaction leading to the implant’s degradation. This response would result in tissue reinforcement that is short-lived.

TEI Products:

TEI’s products do not trigger a detrimental foreign-body inflammatory reaction known to degrade dermal matrices upon implantation or application. The muted inflammatory response is a direct result of the purity of our devices, which contain only 100% non-denatured Type I and Type III collagen.

    •  Our sophisticated biotech process incorporates a solid phase extraction process, utilizing up to 300 liters of purifying solution per cm2 of ADM to remove trace contaminants.

    •  Our products are free of potentially antigenic antibiotics and polysorbate 20 as additives. This, combined with the fact that our process ensures full removal of contaminants and renders our products terminally sterile, contributes to the non-inflammatory nature of our devices.

TEI’s products are built on a platform technology, the purity of which allows our products to be applied to the human brain in dura mater repair.

•  Host-Implant Interactions

Relevance:

Host-implant interactions can have significant impact on soft tissue repair and, therefore, on both short- and long-term clinical outcomes.

There are five possible biological responses when an Acellular Dermal Matrix (ADM) or polymer mesh implant is introduced into a host. They are divided into two categories:

1. ADM (or polymer mesh) non-incorporating responses

    •  Encapsulation

    •  Rejection

2. ADM incorporating responses

    •  Resorption

    •  Integration with progressive degradation

    •  Adoption and adaptation

ADM (or Polymer Mesh) Non-Incorporating Responses:

Encapsulation

In this host-implant interaction, foreign-body giant cells wall-off the foreign object with a layer of dense connective tissue. Those most familiar with this type of host-implant interaction are accustomed to using polymer meshes or sutures, which are permanent synthetic or plastic materials. The acute and chronic inflammatory profile of crosslinked dermis has been known to be consistent with that of this classic foreign-body response to non-resorbable biomaterials, which end without incorporation, but rather in fibrous encapsulation.

Rejection

In contrast to foreign-body response interactions described under “encapsulation,” a rejection response is characterized by:

    •  an initial dense accumulation of neutrophils and mononuclear cells located primarily at the edge of the implanted device, with no cell infiltration into the matrix.

    •  followed by a partial to complete degradation of the implant via a robust inflammatory cell reaction, where multinucleated giant cells degrade.

ADM Incorporating Responses:

The term “incorporation” is often used in the discussion of ADM biomaterials, but it is without a clear definition. We define incorporation as the ability of an ADM biomaterial to repopulate with host cells and revascularize with host blood vessels. This process sees cells penetrate and populate the ADM, and produce proteins and enzymes to simultaneously break down collagen fibers and reassemble collagen fibers to replace the tissue.

Resorption

This host-implant interaction speaks to how biomaterials are rapidly resorbed by the host. Biomaterials undergoing this reaction are swiftly infiltrated by inflammatory cells after as little as seven days. This strong inflammatory response leads to a rapid resorption of the material and replacement with disorganized scar tissue.

Integration with progressive degradation

This response may be witnessed with non-crosslinked ADM biomaterial derived from minimally processed human cadaveric dermis. An early inflammatory response at seven days is marked by dense layers of mononuclear cells at the periphery of the device. Cells surround the device and penetrate the outer layers of the implant slowly causing it to degrade. The material is slowly degraded from the periphery toward the center of the implant and partially replaced with fibrous connective tissue.

Adoption and adaptation

Encapsulation and degradation are not the only results in the use of ADM biomaterials. Some non–crosslinked ADM biomaterials demonstrate adoption by host fibroblasts, and can persist as a new, generative tissue (gTissue), being adapted as necessary to meet the demands of the mechanical loading environment. At the time of implantation, the highly porous material readily traps blood, acting as a sponge to trap cells, growth factors, and cytokines to seed the matrix. The biomaterial is rapidly repopulated with host cells and supporting vasculature. Only a muted inflammatory response in comparison occurs.

What results is living connective tissue, adopted by the host (i.e. populated with fibroblasts), without inflammation, change in cell quantity, or major alteration in the larger collagen fiber architecture.

TEI Products:

TEI’s products follow the “adoption and adaption” model. When implanted, our technology’s purity, sterility, and nativity minimize detrimental foreign-body inflammation to provide a matrix that is revascularized and repopulated with patient cells for prolonged reinforcement during healing.

SurgiMend, for example, unlike synthetic or many other biologic meshes, undergoes neither the encapsulation nor the degradation type of host–implant interaction. It does not elicit an acute or chronic foreign-body inflammatory response leading to the implant’s degeneration. It is adopted by host fibroblasts, rapidly revascularized, and can persist as a new, generative tissue for extended times.

Competitive Products:

Competitive products are derived from sources that include cadaveric or donated human dermis, adult porcine and equine, and whose origins include heart valves, dermis, pericardium, and components of the intestine. Host-implant interactions include encapsulation and rejection. To better understand the host-implant interactions of various competitive products, please review the “host-implant interactions” section of the reference article, “Extracellular Matrix Biomaterials for Soft Tissue Repair.”

(Click here for link to abstract.)